去势抵抗性前列腺癌进展时间的预测因素分析

目的：探索前列腺癌经内分泌治疗后进入去势抵抗性前列腺癌（castration-resistant prostate cancer, CRPC）的预测因素，以更好地指导临床和提高患者预后。方法：回顾性分析了2003年1月至2014年12月在北京大学第一医院泌尿外科确诊前列腺癌并且初始治疗为内分泌治疗的患者共185例，收集并整理分析的临床信息包括患者年龄、前列腺癌TNM分期、前列腺癌病理Gleason评分（Gleason score, GS)、前列腺癌危险度、内分泌治疗开始时前列腺特异性抗原（prostate-specific antigen, PSA）水平、经过内分泌治疗后的PSA最低值、PSA下降速率以及降到PSA最低值的时间。应用Kaplan-Meier生存分析和log-rank检验比较不同分组间CRPC进展时间的差异，应用Cox风险比例回归模型来分析评估这些因素对CRPC进展时间的影响。结果：185例患者平均年龄(71.02±8.67)岁，CRPC进展的中位时间为38个月（4~158个月）。单因素分析中，前列腺癌T分期、N分期、前列腺癌危险度、内分泌治疗前是否发生远处转移、PSA下降速率和PSA最低值均与CRPC进展时间显著相关（P值均小于0.01）。在多因素分析中，内分泌治疗前已发生远处转移（HR=6.030，95% CI：3.229~11.263，P=0.001）、较高的PSA最低值（HR=1.185，95% CI：1.080~1.301，P=0.001）、PSA下降速率>11 μg/(L·month)（HR=2.124，95% CI：1.195~3.750，P=0.001）以及到达PSA最低值的时间≤9个月（HR=3.623，95% CI：1.640~4.817，P=0.004）均是CRPC进展时间较短的危险因素。结论：前列腺癌患者经过内分泌治疗后，PSA下降速率越快，进入CRPC时间越短。

Predictive factor analysis of time to progression of castration-resistant prostate cancer after androgen deprivation therapy

Objective: To explore risk factors including prostate-specific antigen (PSA) kinetics for the prediction of castration-resistant prostate cancer (CRPC), and to build a practical model for predicting the progression to CRPC after androgen deprivation therapy(ADT) so as to facilitate clinicians in decision-making for prostate cancer patients receiving ADT.Methods: A total of 185 patients with prostate cancer who had received ADT as the primary therapy in Department of Urology of Peking University First Hospital from 2003 to 2014 were enrolled retrospectively.All the patients were diagnosed with prostate cancer via prostate biopsy and followed up every four weeks from the initiation of ADT.All the patients received ADT with luteinizing hormone-releasing hormone agonists (LHRH-A) or surgical castration accompanied with an antiandrogen (bicalutamide or flutamide, combined androgen blockade).The clinical information of the patients were collected including age, clinical TNM stage, Gleason score (GS), risk groups of prostate cancer, PSA at the initiation of ADT, PSA nadir after ADT, PSA decline velocity, and the time to PSA nadir.The end point of this study was the diagnosis of CRPC, which was based on the European Association of Urology (EAU) Guideline 2016.Cox proportional hazards regression models were established to analyze and estimate their effects on the time of progression to CRPC.Results: In this study, 185 patients with prostate cancer who had received ADT as the primary therapy were included.The mean age was (71.02±8.67) years.The median time to progression to CRPC in this cohort was 38 months (ranging from 4 to 158 months).On univariate analysis, we found clinical T stage, N stage, the metastasis state before ADT, risk groups of prostate cancer, PSA decline velocity, and PSA nadir were all related to the time to CRPC progression, P<0.01 for all the above variables.And on multivariate analysis, the presence of distant metastasis before ADT (HR=6.030, 95% CI: 3.229-11.263, P=0.001), higher PSA nadir (HR=1.185, 95% CI: 1.080-1.301, P=0.001), higher PSA decline velocity>11 μg/(L·month) (HR=2.124, 95% CI: 1.195-3.750, P=0.001), and time to PSA nadir ≤ 9 months (HR=3.623, 95% CI: 1.640-4.817, P=0.004) were found to be significantly associated with an increased risk of progression to CRPC.Conclusion: Patients with rapid decreasing of PSA in the initial ADT were more likely to progress to CRPC.